Stem Cell Reports最新文献_第6页

Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson's disease. 在帕金森病啮齿动物模型中，运动促进人类干细胞来源的神经移植物的功能整合。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-24 DOI: 10.1016/j.stemcr.2025.102480

Niamh Moriarty, Tyra D Fraser, Cameron P J Hunt, Georgia Eleftheriou, Jessica A Kauhausen, Lachlan H Thompson, Clare L Parish

{"title":"Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson's disease.","authors":"Niamh Moriarty, Tyra D Fraser, Cameron P J Hunt, Georgia Eleftheriou, Jessica A Kauhausen, Lachlan H Thompson, Clare L Parish","doi":"10.1016/j.stemcr.2025.102480","DOIUrl":"10.1016/j.stemcr.2025.102480","url":null,"abstract":"Human pluripotent stem cell (hPSC)-derived dopamine neurons can functionally integrate and reverse motor symptoms in Parkinson's disease models, motivating current clinical trials. However, dopamine neuron proportions remain low and their plasticity inferior to fetal tissue grafts. Evidence shows exercise can enhance neuron survival and plasticity, warranting investigation for hPSC-derived neural grafts. We show voluntary exercise (wheel running) significantly increases graft plasticity, accelerating motor recovery in animals receiving ectopic, but not homotopic, placed grafts, suggestive of threshold requirements. Plasticity was accompanied by increased phosphorylated extracellular signal-regulated kinase (ERK+) cells in the graft (and host), reflective of mitogen-activated protein kinase (MAPK)-ERK signaling, a downstream target of glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), proteins that were also elevated. Verifying improved graft integration was the increase in cFos+ postsynaptic striatal neurons. These findings have direct implications for the adoption of physical therapy-based approaches to enhance neural transplantation outcomes in future Parkinson's disease clinical trials.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102480"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MIXL1 activation in endoderm differentiation of human induced pluripotent stem cells. MIXL1在人诱导多能干细胞内胚层分化中的激活。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-24 DOI: 10.1016/j.stemcr.2025.102482

Pierre Osteil, Sarah Withey, Nicole Santucci, Nader Aryamanesh, Ignatius Pang, Nazmus Salehin, Jane Sun, Annie Qin, Jiayi Su, Hilary Knowles, Xiucheng Bella Li, Simon Cai, Ernst Wolvetang, Patrick P L Tam

引用次数: 0

Language and labels from the lab: Definitions in the stem cell-based embryo model debate. 来自实验室的语言和标签：基于干细胞的胚胎模型辩论中的定义。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-17 DOI: 10.1016/j.stemcr.2025.102477

Hafez Ismaili M'hamdi

引用次数: 0

Perinuclear mitochondrial clustering for mesenchymal-to-epithelial transition in pluripotency induction. 多能诱导中间质向上皮转化的核周线粒体聚类。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-17 DOI: 10.1016/j.stemcr.2025.102474

Ge Xiang, Zihuang Liu, Zebin Yuan, Zhongfu Ying, Yingzhe Ding, Dongtong Lin, Haihao Qin, Shanshan Dong, Shihe Zhou, Hao Yuan, Wei Xie, Zhihong Zheng, Yongqiang Chen, Linpeng Li, Qi Long, Liang Yang, Yi Wu, Keshi Chen, Feixiang Bao, Yile Huang, Wei Li, Junwei Wang, Yang Liu, Dajiang Qin, Xingguo Liu

{"title":"Perinuclear mitochondrial clustering for mesenchymal-to-epithelial transition in pluripotency induction.","authors":"Ge Xiang, Zihuang Liu, Zebin Yuan, Zhongfu Ying, Yingzhe Ding, Dongtong Lin, Haihao Qin, Shanshan Dong, Shihe Zhou, Hao Yuan, Wei Xie, Zhihong Zheng, Yongqiang Chen, Linpeng Li, Qi Long, Liang Yang, Yi Wu, Keshi Chen, Feixiang Bao, Yile Huang, Wei Li, Junwei Wang, Yang Liu, Dajiang Qin, Xingguo Liu","doi":"10.1016/j.stemcr.2025.102474","DOIUrl":"10.1016/j.stemcr.2025.102474","url":null,"abstract":"Remodeled mitochondria are characteristic of pluripotent stem cells. However, a role for mitochondrial movement and distribution in pluripotency remains unknown. Here, we show that mitochondrial retrograde transport-mediated perinuclear clustering via dynein complex occurs at the early phase of pluripotency induction. Interestingly, this mitochondrial redistribution is regulated by Yamanaka factor OCT4 but not SOX2 or KLF4. This mitochondrial redistribution, which has effect on the efficiency of somatic cell reprogramming, also depends on DRP1-mediated mitochondrial fission. Importantly, perinuclear mitochondrial clustering is required for mesenchymal-to-epithelial transition (MET), an early step in reprogramming, during which β-catenin regulates the MET process. Furthermore, sufficient amount of β-catenin plays a key role in maintaining stabilization of E-CADHERIN. Taken together, these studies show that perinuclear mitochondrial clustering is an essential organellar step for MET process of pluripotency induction, which may shed light on the subcellular relationship between mitochondrial dynamics, pluripotency, and cellular morphology.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102474"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation. 在女性hiPSCs中，X染色体失活后的基因再激活是可预测的，但也是可变的，并通过分化持续存在。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-03 DOI: 10.1016/j.stemcr.2025.102472

Ana Cláudia Raposo, Paulo Caldas, Joana Jeremias, Maria Arez, Francisca Cazaux Mateus, Pedro Barbosa, Rui Sousa-Luís, Frederico Água, David Oxley, Annalisa Mupo, Melanie Eckersley-Maslin, Miguel Casanova, Ana Rita Grosso, Simão Teixeira da Rocha

{"title":"Gene reactivation upon erosion of X chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation.","authors":"Ana Cláudia Raposo, Paulo Caldas, Joana Jeremias, Maria Arez, Francisca Cazaux Mateus, Pedro Barbosa, Rui Sousa-Luís, Frederico Água, David Oxley, Annalisa Mupo, Melanie Eckersley-Maslin, Miguel Casanova, Ana Rita Grosso, Simão Teixeira da Rocha","doi":"10.1016/j.stemcr.2025.102472","DOIUrl":"10.1016/j.stemcr.2025.102472","url":null,"abstract":"Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by X-inactive specific transcript (XIST) RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding of its impact on stem cell applications. Here, we show that XCI erosion is frequent and heterogeneous, leading to the reactivation of several X-linked genes. These are primarily located on the short arm of the X chromosome, particularly near escape genes and within H3K27me3-enriched domains, with reactivation linked to reduced promoter DNA methylation. Interestingly, escape genes further increase their expression from Xi upon XCI erosion, highlighting the critical role of XIST in their dosage regulation. Importantly, global (hydroxy)methylation levels and imprinted regions remain unaffected, and analysis of trilineage commitment and cardiomyocyte formation reveals that XCI erosion persists across differentiation. These findings underscore the need for greater awareness of the implications of XCI erosion for stem cell research and clinical applications.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102472"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safeguarding genomic imprints in naive human pluripotency. 保护人类多能性的基因组印记。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-17 DOI: 10.1016/j.stemcr.2025.102475

Alejandro De Los Angeles

引用次数: 0

What does "appropriate scientific justification" mean for the review of human pluripotent stem cell, embryo, and related research? 对于人类多能干细胞、胚胎和相关研究的审查，“适当的科学理由”意味着什么？

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-04-24 DOI: 10.1016/j.stemcr.2025.102479

Erica C Jonlin, Misao Fujita, Rosario Isasi, Kazuto Kato, Megan Munsie, Kaori Muto, Kathy Niakan, Krishanu Saha, Jeremy Sugarman, Leigh Turner, Insoo Hyun

引用次数: 0

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-05-13 Epub Date: 2025-03-28 DOI: 10.1016/j.stemcr.2025.102478

Jacob A Klickstein, Michelle A Johnson, Pantelis Antonoudiou, Jamie Maguire, Joao A Paulo, Steve P Gygi, Chris Weihl, Malavika Raman

引用次数: 0

Single-cell multiomic comparison of mouse and rat spermatogenesis reveals gene regulatory networks conserved for over 20 million years. 小鼠和大鼠精子发生的单细胞多组学比较揭示了保存超过2000万年的基因调控网络。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-13 DOI: 10.1016/j.stemcr.2025.102449

Eoin C Whelan, John J Swain, Jonathan H Sussman, David Smith, Fan Yang, Antonia Rotolo, Mary R Avarbock, Clara Malekshahi, Enrico Radaelli, Daniel P Beiting, Ralph L Brinster

{"title":"Single-cell multiomic comparison of mouse and rat spermatogenesis reveals gene regulatory networks conserved for over 20 million years.","authors":"Eoin C Whelan, John J Swain, Jonathan H Sussman, David Smith, Fan Yang, Antonia Rotolo, Mary R Avarbock, Clara Malekshahi, Enrico Radaelli, Daniel P Beiting, Ralph L Brinster","doi":"10.1016/j.stemcr.2025.102449","DOIUrl":"10.1016/j.stemcr.2025.102449","url":null,"abstract":"Spermatogenesis is driven by dramatic changes in chromatin regulation, gene transcription, and protein expression. To assess the mechanistic bases for these developmental changes, we utilized multiomic single-cell/nucleus RNA sequencing (sc/snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to identify chromatin changes associated with transcription in adult mouse and rat testes. We characterized the relationships between the transcriptomes and chromatin of both species, including the divergent expression of Id4 in spermatogonial stem cells between species. Promoter accessibility and gene expression showed the greatest association during meiosis in both species. We mapped the cross-species conservation of putative regulatory regions for key spermatogenic genes, including Cd9 and Spam1, and investigated correlations and disconnects in chromatin accessibility, gene expression, and protein expression via antibody-derived tags. Using a gene regulatory network (GRN) model, we identified 40 core regulons conserved between mouse and rat germ cells, highlighting the relevance of chromatin-related factors in regulating the transcription of canonical genes across spermatogenesis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102449"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic remodeling in hiPSC-derived myofibers carrying the m.3243A>G mutation. 携带m.3243A>G突变的hipsc来源肌纤维的代谢重塑。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-04-08 Epub Date: 2025-03-13 DOI: 10.1016/j.stemcr.2025.102448

Gabriel E Valdebenito, Anitta R Chacko, Chih-Yao Chung, Preethi Sheshadri, Haoyu Chi, Benjamin O'Callaghan, Monika J Madej, Henry Houlden, Hannah Rouse, Valle Morales, Katiuscia Bianchi, Francesco Saverio Tedesco, Robert D S Pitceathly, Michael R Duchen

{"title":"Metabolic remodeling in hiPSC-derived myofibers carrying the m.3243A>G mutation.","authors":"Gabriel E Valdebenito, Anitta R Chacko, Chih-Yao Chung, Preethi Sheshadri, Haoyu Chi, Benjamin O'Callaghan, Monika J Madej, Henry Houlden, Hannah Rouse, Valle Morales, Katiuscia Bianchi, Francesco Saverio Tedesco, Robert D S Pitceathly, Michael R Duchen","doi":"10.1016/j.stemcr.2025.102448","DOIUrl":"10.1016/j.stemcr.2025.102448","url":null,"abstract":"Mutations in mitochondrial DNA cause severe multisystem disease frequently associated with muscle weakness. The m.3243A>G mutation is the major cause of mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). Experimental models that recapitulate the disease phenotype in vitro for disease modeling or drug screening are very limited. We have therefore generated hiPSC-derived muscle fibers with variable heteroplasmic mtDNA mutation load without significantly affecting muscle differentiation potential. The cells exhibit physiological characteristics of muscle fibers and show a well-organized myofibrillar structure. In cells carrying the m.3243A>G mutation, the mitochondrial membrane potential and oxygen consumption were reduced in relation to the mutant load. We have shown through proteomic, phosphoproteomic, and metabolomic analyses that the m.3243A>G mutation variably affects the cell phenotype in relation to the mutant load. This variation is reflected by an increase in the NADH/NAD+ ratio, which in turn influences key nutrient-sensing pathways in the myofibers. This model enables a detailed study of the impact of the mutation on cellular bioenergetics and on muscle physiology with the potential to provide a platform for drug screening.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102448"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0